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diabetic foot syndrome:Immune-inflammatory features as possible cardiovascular markers in diabetes

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World Journal of Orthopedics 2015年第1期6卷 62-76页

作者： Antonino Tuttolomondo Carlo Maida Antonio Pinto dipartimento Biomedico di medicina Interna e specialistica U.O.C di Medicina Interna e CardioangiologiaUniversità degli Studi di Palermo

diabetic foot ulcerations have been extensively reported as vascular complications of diabetes mellitus associated with a high degree of morbidity and mortality. diabetic foot syndrome(DFS), as defined by the World Health Organization, is an "ulceration of the foot(distally from the ankle and including the ankle) associated with neuropathy and different grades of ischemia and infection". Pathogenic events able to cause diabetic foot ulcers are *** the commonest causes of this pathogenic pathway it's possible to consider peripheral neuropathy, foot deformity, abnormal foot pressures, abnormal joint mobility, trauma, peripheral artery disease. Several studies reported how diabetic patients show a higher mortality rate compared to patients without diabetes and in particular these studies under filled how cardiovascular mortality and morbidity is 2-4 times higher among patients affected by type 2 diabetes mellitus. This higher degree of cardiovascular morbidity has been explained as due to the observed higher prevalence of major cardiovascular risk factor, of asymptomatic findings of cardiovascular diseases, and of prevalence and incidence of cardiovascular and cerebrovascular events in diabetic patients with foot complications. In diabetes a fundamental pathogenic pathway of most of vascular complications has been reported as linked to a complex interplay of inflammatory, metabolic and procoagulant variables. These pathogenetic aspects have a direct interplay with an insulin resistance, subsequent obesity, diabetes, hypertension, prothrombotic state and blood lipid disorder. Involvement of inflammatory markers such as IL-6 plasma levels and resistin in diabetic subjects as reported by Tuttolomondo et al confirmed the pathogenetic issue of the a "adipo-vascular" axis that may contribute to cardiovascular risk in patients with type 2 diabetes. This "adipo-vascular axis" in patients with type 2 diabetes has been reported as characterized by lower plasma l

关键词： diabetic foot syndrome Inflammation Cytokines Cardiovascular risk Marker

De novo autoimmune hepatitis in liver transplant: State-of-the-art review

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World Journal of Gastroenterology 2016年第10期22卷 2906-2914页

作者： Ranka Vukotic Giovanni Vitale Antonia D'Errico-Grigioni Luigi Muratori Pietro Andreone dipartimento di Scienze Mediche e Chirurgiche Università di BolognaPoliclinico Sant’Orsola-Malpighi dipartimento di medicina specialistica Diagnostica e SperimentaleUniversità di Bologna"F.Addarii" Institute of Oncology and Transplantation PathologyPoliclinico Sant’Orsola-Malpighi

In the two past decades, a number of communications, case-control studies, and retrospective reports have appeared in the literature with concerns about the development of a complex set of clinical, laboratory and histological characteristics of a liver graft dysfunction that is compatible with autoimmune hepatitis. The de novo prefix was added to distinguish this entity from a pre-transplant primary autoimmune hepatitis, but the globally accepted criteria for the diagnosis of autoimmune hepatitis have been adopted in the diagnostic algorithm. Indeed, de novo autoimmune hepatitis is characterized by the typical liver necroinflammation that is rich in plasma cells, the presence of interface hepatitis and the consequent laboratory findings of elevations in liver enzymes, increases in serum gamma globulin and the appearance of nonorgan specific auto-antibodies. Still, the overall features of de novo autoimmune hepatitis appear not to be attributable to a univocal patho-physiological pathway because they can develop in the patients who have undergone liver transplantation due to different etiologies. Specifically, in subjects with hepatitis C virus recurrence, an interferon-containing antiviral treatment has been indicated as a potential inception of immune system derangement. Herein, we attempt to review the currently available knowledge about de novo liver autoimmunity and its clinical management.

关键词： De novo autoimmune hepatitis Plasma-cell hepatitis Liver transplant Hepatitis C virus recurrence Antiviral therapy Autoimmunity differential diagnosis

clinical course and prognostic factors of hepatorenal syndrome:a retrospective single-center cohort study

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World Journal of Hepatology 2013年第12期5卷 685-691页

作者： Anna Licata Marcello Maida Ambra Bonaccorso Fabio Salvatore Macaluso Maria Cappello Antonio Craxì Piero Luigi Almasio Section of Gastroenterology Dipartimento Biomedicodi Medicina Interna e SpecialisticaUniversity of Palermo

AIM: To investigate clinical and biochemical features of hepatorenal syndrome(HRS), to assess short and long- term survival evaluating potential predictors of early mortality. METHODS: Sixty-two patients with liver cirrhosis and renal failure, defined as a serum creatinine value > 1.5 mg/dL on at least two measurements within 48 h, admitted to our tertiary referral Unit from 2001 to 201, were retrospectively reviewed. Among them, 33 patients(53.2%) fulfilled the revised criteria of the International Ascites Club for the diagnosis of HRS. Twenty-eight patients were treated with combinations of terlipressin and albumin, two with dopamine and al- bumin, and three with albumin alone. No patients were suitable for liver transplantation. Complete response was defined as normalization of creatinine levels to less than 1.5 mg/dL, partial response as a decrease of at least 50% but not to less than 1.5 mg/dL, no response as no reduction in creatinine or a decrease of less 50% compared to pre-treatment values. All of the patients were followed up for at least 1 year until January 2013. RESULTS: HRS type 1 was diagnosed in 15 patients(45.5%). Hepatitis C virus infection was the primary etiology(69.6%), followed by alcohol(15.2%), and cryptogenesis(15.2%). Complete response to therapy was obtained in only 3 cases(9.1%) and partial re- sponse in 7 patients(21.2%). Median survival was 30 d(range: 10-274) without significant differences be- tween type 1 and type 2 HRS. By univariate analysis, Child-Pugh class C(P = 0.009), presence of hepatocel- lular carcinoma(P = 0.04), low serum sodium(P = 0.02), high bilirubin values(P = 0.009) and high Model for End-stage Liver disease(MELD) score(P = 0.03) were predictive factors of 30-d mortality. By multivari- ate analysis, only serum sodium 27(OR = 18.72; P = 0.01) were independently associated with a survival of less than one month. CONCLUSION: HRS still has a poor prognosis, even when va

关键词： Hepatorenal syndrome Liver cirrhosis Hepatitis C virus vasoactive drugs Mortality

Finding a way to preserve mitochondria: new pathogenic pathways in experimental multiple sclerosis

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Neural Regeneration Research 2019年第1期14卷 77-78页

作者： Andrea Mancini Lorenzo Gaetani Lucia Gentili Massimiliano di Filippo Clinica Neurologica Dipartimento di Medicina Università degli Studi di Perugia

Multiple sclerosis(MS)is a chronic disorder affecting central nervous system(CNS)in which inflammatory and neuro-degenerative features coexist since the earlier phases of the disease(Reich et al.,2018).During last years,attention has been directed toward the possible pathogenic pathways linking these two different features characterizing MS,in order to acquire a better understanding of the disease pathogenesis and to design new disease modifying *** available therapies for MS are primarily

关键词：小径病原硬化多重试验性线粒体保存疾病

Follicular lymphoma:the diminishing role of chemotherapy

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Journal of Cancer Metastasis and Treatment 2022年第1期8卷 393-411页

作者： Beatrice Casadei Laura Nanni Ginevra Lolli Pier Luigi Zinzani IRCCS Azienda Ospedaliero-Universitaria di Bologna Istituto di Ematologia“Seràgnoli”Bologna 40138Italy dipartimento di medicina specialistica Diagnostica e SperimentaleUniversitàdi BolognaBologna 40138Italy

Follicular lymphoma(FL)is the most common indolent non-Hodgkin lymphoma,accounting for 70%of cases in Western *** this unique name,FL is an extremely heterogeneous disease,both clinically and *** basis of FL heterogeneity lies in the different biological pathways which can be activated,because of the variety of gene mutations that can ***,there is a growing interest in the knowledge of these activated pathways,which is also testified by the presence of a new model that incorporates FL mutations to define patient’s prognosis(m7-FLIPI).These evaluations are also appealing because of the recent possibility of using“targeted therapies”.Targeted therapies are new tools,currently applicable in the setting of relapse/refractory(R/R)disease,where we can find a great variety of“chemo-free”*** in other hematologic malignancies,“cellular therapy”enriches FL drug scenario,including T-cell dependent bispecific antibodies and chimeric antigen receptor(CAR)*** FL heterogeneity is the basis of the difference in therapeutic efficacy and disease course among patients,the hope for the future is to understand FL biology more deeply,to better comprehend how to obtain more representative samples and pre-treatment prognostic information in order to individualize the treatment strategy as early as frontline therapy.

关键词： Follicular lymphoma POD24 target therapies chemo-immunotherapy biological heterogeneity

Adalimumab efficacy in enteropathic spondyloarthritis: A 12-mo observational multidisciplinary study

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World Journal of Gastroenterology 2017年第39期23卷 7139-7149页

作者： Michele Maria Luchetti Devis Benfaremo Francesco Ciccia Laura Bolognini Monia Ciferri Alessia Farinelli Matteo Rossini Piergiorgio Mosca Giovanni Triolo Armando Gabrielli dipartimento Scienze Cliniche e Molecolari Clinica MedicaUniversità Politecnica delle Marche dipartimento Biomedico di medicina Interna e specialistica Sezione di Reumatologia Università degli Studi di Palermo dipartimento Gastro-enterologico e dei Trapianti Polo Ospedaliero--Universitario 'Umberto I-G.M. Lancisi- G. Salesi'

AIM To report adalimumab(Ada) efficacy on articulargastrointestinal disease and health-related quality of life(HRQo L) in patients with enteropathic spondyloarthritis(ES).METHODS A cohort of 52 patients with ES was evaluated in the departments of gastroenterology and internal medicine. At baseline, all patients underwent assessment by an integrated gastro-rheumatologic evaluation of articular and gastrointestinal activity, as well patient reported outcomes(PROs) of the HRQo L questionnaires. After this integrated evaluation and following a specific working flowchart, the Ada anti-tumor necrosis factor(TNF)-inhibitor was assigned to a cohort of 30 patients and its clinical efficacy was evaluated at baseline and after 6-mo and 12-mo treatment by the following tests:(1) Ankylosing Spondylitis disease Activity ScoreC-Reactive Protein(ASDAS-CRP); Bath Ankylosing Spondylitis disease Activity Index(BASDAI), Bath Ankylosing Spondylitis Functional Index(BASFI) and Bath Ankylosing Spondylitis Metrology Index(BASMI) for articular activity;(2) Inflammatory Bowel disease Questionnaire(IBDQ), Crohn's disease Activity Index(CDAI) and partial Mayo(p Mayo) score for gastrointestinal symptoms and activity; and(3) Health Assessment Questionnaire(HAQ), Patient Global Assessment(PGA) and Short Form-36 health survey(SF-36) questionnaires for PROs of the HRQo *** Integrated evaluation and management of the patients affected by ES, carried out simultaneously by a gastroenterologist and a rheumatologist, allowed clinicians to choose the optimal therapeutic strategy. In a cohort of 30 ES patients affected by active articular and gastrointestinal disease, or axial active articular inflammation, Ada led to fast and sustained improvement of both articular and gastrointestinal disease activities. In fact, all the clinimetric evaluation tests exploring articular or gastrointestinal activity, as well as all the HRQo L scores, showed a significant improvement having been achieved at the earli

关键词： Clinimetric assessment Patient reported outcomes Inflammatory bowel diseases Enteropathic spondyloarthritis Tumor necrosis factor-inhibitors Multidisciplinary evaluation

Changes in nutritional status after liver transplantation

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World Journal of Gastroenterology 2014年第31期20卷 10682-10690页

作者： Michela Giusto Barbara Lattanzi Vincenza di Gregorio Valerio Giannelli Cristina Lucidi Manuela Merli Ⅱ Gastroenterologia Dipartimento di Medicina Clinica "Sapienza" Università di Roma00185 Roma Italy

Chronic liver disease has an important effect on nutritional status, and malnourishment is almost universally present in patients with end-stage liver disease who undergo liver transplantation. During recent decades,a trend has been reported that shows an increase in number of patients with end-stage liver disease and obesity in developed countries. The importance of carefully assessing the nutritional status during the workup of patients who are candidates for liver replacement is widely recognised. Cirrhotic patients with depleted lean body mass(sarcopenia) and fat deposits have an increased surgical risk; malnutrition may further impact morbidity, mortality and costs in the post-transplantation setting. After transplantation and liver function is restored, many metabolic alterations are corrected,dietary intake is progressively normalised, and lifestyle changes may improve physical activity. Few studies have examined the modifications in body composition that occur in liver recipients. During the first 12 mo, the fat mass progressively increases in those patients who had previously depleted body mass, and the muscle mass recovery is subtle and non-significant by the end of the first year. In some patients, unregulated weight gain may lead to obesity and may promote metabolicdisorders in the long term. Careful monitoring of nutritional changes will help identify the patients who are at risk for malnutrition or over-weight after liver transplantation. Physical and nutritional interventions must be investigated to evaluate their potential beneficial effect on body composition and muscle function after liver transplantation.

关键词： Liver transplantation Sarcopenia Malnutrition Obesity Metabolic syndrome Outcome Survival

challenges of advanced hepatocellular carcinoma

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World Journal of Gastroenterology 2016年第34期22卷 7645-7659页

作者： Stefano Colagrande Andrea L Inghilesi Sami Aburas Gian G Taliani Cosimo Nardi Fabio Marra dipartimento di Scienze Biomediche Sperimentali e Cliniche University of Florence dipartimento di medicina Sperimentale e Clinica Centro di Ricerca DenotheUniversity of Florence

Hepatocellular carcinoma(HCC) is an aggressive malignancy,resulting as the third cause of death by cancer each year. The management of patients with HCC is complex,as both the tumour stage and any underlying liver disease must be considered conjointly. Although surveillance by imaging,clinical and biochemical parameters is routinely performed,a lot of patients suffering from cirrhosis have an advanced stage HCC at the first diagnosis. Advanced stage HCC includes heterogeneous groups of patients with different clinical condition and radiological features and sorafenib is the only approved treatment according to Barcelona Clinic Liver Cancer. Since the introduction of sorafenib in clinical practice,several phase Ⅲ clinical trials have failed to demonstrate any superiority over sorafenib in the frontline setting. Locoregional therapies have also been tested as first line treatment,but their role in advanced HCC is still matter of debate. No single agent or combination therapies have been shown to impact outcomes after sorafenib failure. Therefore this review will focus on the range of experimental therapeutics for patients with advanced HCC and highlights the successes and failures of these treatments as well as areas for future development. Specifics such as dose limiting toxicity and safety profile in patients with liver dysfunction related to the underlying chronic liver disease should be considered when developing therapies in HCC. Finally,robust validated and reproducible surrogate end-points as well as predictive biomarkers should be defined in future randomized trials.

关键词： Barcelona Clinic Liver Cancer Portal vein thrombosis Modified Response Evaluation Criteria in Solid Tumors Advanced hepatocellular carcinoma management Advanced hepatocellular carcinoma second line therapies Sorafenib

Proteinase activated-receptors-associated signaling in the control of gastric cancer

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World Journal of Gastroenterology 2014年第34期20卷 11977-11984页

作者： Silvia Sedda Irene Marafini Roberta Caruso Francesco Pallone Giovanni Monteleone dipartimento di medicina dei Sistemi Università Tor Vergata00133 RomeItaly

Gastric cancer(GC)is the fourth most common cancer in the world and the second cause of cancer-related *** carcinogenesis is a multifactorial process,in which environmental and genetic factors interact to activate multiple intracellular signals thus leading to uncontrolled growth and survival of GC *** such a pathway is regulated by proteinase activated-receptors(PARs),seven transmembrane-spanning domain G protein-coupled receptors,which comprise four receptors(i.e.,PAR-1,PAR-2,PAR-3,and PAR-4)activated by various *** PAR-1 and PAR-2 are over-expressed on GC cells and their activation triggers and/or amplifies intracellular pathways,which sustain gastric *** is also evidence that expression of either PAR-1 or PAR-2 correlates with depth of wall invasion and metastatic dissemination and inversely with the overall survival of ***,data emerging from experimental models of GC suggest that both these receptors can be important targets for therapeutic interventions in GC *** contrast,PAR-4levels are down-regulated in GC and correlate inversely with the aggressiveness of GC,thus suggesting a negative role of this receptor in the control of *** this article we review the available data on the expression and role of PARs in GC and discuss whether manipulation of PAR-driven signals may be useful for interfering with GC cell behavior.

关键词： Proteinase activated-receptors Gastric cancer Helicobacter pylori infection